Total Synthesis of (+)-Paucidactine D

The first total synthesis of (+)-paucidactine D (4) is detailed from the pentacyclic intermediate 13. The approach features two bridging cyclizations with the first being a SmI₂-mediated intramolecular C21-C2 free radical cyclization to access the highly substituted bicyclo[2.2.2]octane core ring system. A subsequent intramolecular S_N2 displacement reaction was used to establish the C11-O bond of the bridging C11-OC(O)-C3 six-membered lactone. Central to the assemblage of the underlying Aspidosperma skeleton of 13 is a powerful [4 + 2]/[3 + 2] cycloaddition cascade of 1,3,4-oxadiazole 15, which provided the highly functionalized pentacyclic ring system in one step as a single diastereomer. The efforts combined with our past studies now represent the divergent total syntheses of members of eight distinct naturally occurring alkaloid classes from the same common intermediate 13, with each implementing a different late-stage core strategic bond formation.